What are the considerations for a pregnant woman on methadone (methadone maintenance therapy)?

From the Guidelines

If you are pregnant and on methadone, it is strongly recommended that you continue your methadone treatment under the close supervision of a healthcare provider 1.

Key Considerations

• Abruptly stopping methadone can lead to withdrawal symptoms, which may be harmful to both you and your baby.
• Your healthcare provider may adjust your methadone dose to the lowest effective dose to manage your withdrawal symptoms and cravings, typically in the range of 20-150 mg per day 1.
• It is essential to receive prenatal care and attend regular check-ups to monitor your health and the health of your baby.
• Additionally, your healthcare provider may recommend other medications, such as prenatal vitamins and folate, to support your health and the development of your baby.

Methadone Treatment

• The initial dosage of methadone is usually 20-30 mg and is generally titrated gradually over weeks to a dosage of 80-120 mg per day 1.
• However, some pregnant women will require significantly higher dosages, and adjustments may be needed due to expanded volume of distribution and progesterone-increased cytochrome P450 metabolism of methadone during pregnancy 1.
• Split doses or a dosage increase may be necessary to prevent cravings and withdrawal symptoms during pregnancy, but should not be undertaken at the same time to avoid the risk of methadone overdose 1.

Monitoring and Precautions

• Methadone is known to prolong the corrected QT (QTc) interval, and caution should be taken if QTc is >450-499 msec, with alternative therapy considered if QTc is 500 msec 1.
• An interdisciplinary approach involving the obstetric team and the addiction medicine team or methadone clinic providers should ensure that the woman receives appropriate care and support during labor and delivery 1.

From the FDA Drug Label

Pregnancy Teratogenic Effects – Pregnancy Category C. There are no controlled studies of methadone use in pregnant women However, an expert review of published data on experiences with methadone use during pregnancy by the Teratogen Information System (TERIS) concluded that maternal use of methadone during pregnancy as part of a supervised, therapeutic regimen is unlikely to pose a substantial teratogenic risk (quantity and quality of data assessed as “limited to fair”) Methadone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Pregnant women involved in methadone maintenance programs have been reported to have significantly improved prenatal care leading to significantly reduced incidence of obstetric and fetal complications and neonatal morbidity and mortality Several factors complicate the interpretation of investigations of the children of women who take methadone during pregnancy Methadone has been detected in amniotic fluid and cord plasma at concentrations proportional to maternal plasma and in newborn urine at lower concentrations than corresponding maternal urine Several studies have suggested that infants born to narcotic-addicted women treated with methadone during all or part of pregnancy have been found to have decreased fetal growth with reduced birth weight, length, and/or head circumference compared to controls. Children born to women treated with methadone during pregnancy have been shown to demonstrate mild but persistent deficits in performance on psychometric and behavioral tests.

The considerations for a pregnant woman on methadone maintenance therapy include:

• Potential teratogenic risk: Methadone is classified as Pregnancy Category C, and while there is no substantial evidence of teratogenic risk, the data are insufficient to state that there is no risk.
• Improved prenatal care: Pregnant women in methadone maintenance programs have improved prenatal care, leading to reduced obstetric and fetal complications.
• Fetal growth: Infants born to women treated with methadone may have decreased fetal growth and reduced birth weight, length, and/or head circumference.
• Neonatal withdrawal: Babies born to mothers taking opioids, including methadone, may be physically dependent and experience withdrawal symptoms.
• Psychometric and behavioral deficits: Children born to women treated with methadone during pregnancy may demonstrate mild but persistent deficits in performance on psychometric and behavioral tests.
• Dose adjustment: Pregnant women may require dose adjustments due to changes in methadone pharmacokinetics during pregnancy 2, 2, 2.

From the Research

Considerations for Pregnant Women on Methadone Maintenance Therapy

• Methadone maintenance is the treatment of choice for opioid use disorder during pregnancy, but emerging data indicate buprenorphine is a viable alternative 3
• Pregnant women may require transition from methadone to buprenorphine for maintenance treatment due to costs and limited accessibility of methadone 3
• A standardized protocol using low buprenorphine doses can be implemented to minimize emergent withdrawal symptoms under careful obstetric and psychiatric monitoring 3

Maternal and Neonatal Outcomes

• Pregnant women transitioned from methadone to buprenorphine maintenance showed maternal and neonatal outcomes comparable to studies of women on buprenorphine throughout pregnancy 3
• Infants born to buprenorphine-maintained women who abstained from illicit substances and other prescribed psychotropic medications experienced less severe neonatal abstinence syndrome (NAS) and shorter hospitalizations 3
• Methadone maintenance during pregnancy is associated with a reduced risk of neonatal abstinence syndrome and shorter hospital stays compared to methadone taper or withdrawal 4

Clinical Management

• Nurses should be aware of the clinical management of pregnant women maintained on methadone treatment, including antepartum issues, intrapartum issues, and postpartum concerns such as breastfeeding and neonatal withdrawal 5
• Methadone clearance increases during pregnancy, and trough mean plasma methadone concentrations reduce as the pregnancies progress 6
• Prescribing clinicians should take seriously complaints of methadone withdrawal symptoms from pregnant opioid users and consider a more detailed assessment 6

Breastfeeding and Methadone Maintenance

• Methadone offers significant therapeutic benefits to pregnant, opiate-dependent women, and breastfeeding seems to be safe for women on methadone maintenance 7
• Although amounts of methadone in breast milk appear to be very small, women on methadone do not often breastfeed, for a variety of reasons 7
• Providers should be aware of the issues facing women who elect to breastfeed while on methadone maintenance and provide clinical advice and guidance 7